High beta integrin expression is differentially associated with worsened pancreatic ductal adenocarcinoma outcomes

Outcomes in pancreatic ductal adenocarcinoma (PDAC) are known to be worse in tumors with high integrin β1 expression, but targeted monotherapy against this integrin has not been effective. Seven other beta integrins are expressed in mammalian biology and they are known to have overlapping and compensatory signaling in biological systems. However, their roles in PDAC are poorly understood and have not been systematically compared to integrin β1 biology. In this study, we analyzed the clinical outcomes against beta integrin 1-8 (ITGB1-8) expression in PDAC samples from two large independent cohorts, The Cancer Genome Atlas (TCGA) and {"type":"entrez-geo","attrs":{"text":"GSE21501","term_id":"21501"}}GSE21501. Biological function and tumor microenvironment composition were studied using Gene Set Enrichment Analysis and xCell. Expression of all eight beta integrins is significantly increased in PDACs relative to normal pancreatic tissues (all P<0.001). ITGB1, 2, 5, and 6 have similarly enriched gene patterns related to transforming growth factor (TGF)-β, epithelial mesenchymal transition, inflammation, stemness, and angiogenesis pathways. Homologous recombination defects and neoantigens are increased in high-ITGB4, 5, and 6 tumors, with decreased overall survival in high-ITGB1, 5, and 6 tumors compared to low expression tumors (hazard ratios 1.5-2.0). High-ITGB1, 2, and 5 tumors have increased fibroblast infiltration (all P<0.01) while endothelial cells are increased in high-ITGB2 and 3 tumors (all P<0.05). Overall, beta integrin expression does not correlate to immune cell populations in PDACs. Therefore, while all beta integrins are overexpressed in PDACs, they exert differential effects on PDAC biology. ITGB2, 5, and 6 have a similar profile to ITGB1, suggesting that future research in PDAC integrin therapy needs to consider the complementary signaling profiles mediated by these integrins.     

Serum interleukin 2 receptor levels in childhood acute lymphoblastic leukemia

The clinical significance of interleukin 2 receptor (IL2R) concentrations in serum was determined for 344 children with newly diagnosed acute lymphoblastic leukemia (ALL). Serum levels of IL2R in patients (267 to 80,000 U/mL, median 2,007 U/mL) were significantly higher than normal control values (170 to 738 U/mL, median 347 U/mL) (P less than .0001). Measurements in cases of T cell ALL were lower than in the non-T, non-B cases (P = .02). Among the 264 patients with non-T, non-B ALL, but not in those with T cell disease, higher serum IL2R levels (greater than 2,000 U/mL) were associated with a poorer treatment outcome (P = .04). In a multivariate analysis, serum IL2R level contributed independent prognostic information beyond that conveyed by leukocyte count, race, and age (P = .04). One explanation for these results is that soluble IL2R competes with normal lymphocyte- integrated IL2R for the ligand and thus could suppress host antitumor immunity.     

程序变温法确定药物降解反应级数

通过电子计算机模拟程序升温加速试验,从理论上阐明了常规的程序升温法不能确定药物降解反应级数的原因是因为同一组数据可由不同的反应级数和活化能的组合所拟合;解决这一问题的关键是在一个变温程序中包含升温和降温部分;据此提出了一种新的程序变温方法(程序升降温法)。利用这种方法,可以真正做到只通过一次程序变温加速试验,就获得包括反应级数在内的药物降解的动力学参数,且确定反应级数的能力与恒温法相近似。     

4-芳杂环单/双氨甲基酚衍生物的合成和量化计算

本文在前报的基础上,设计和合成了4-芳杂环取代的氨甲基酚衍生物28个。初步药理试验表明,多数显示不同程度的抗炎活性。用CNDO/2法计算所得数据提示,该类化合物分子中的氨甲基氮和酚羟基氧与受体正电荷中心的结合,可能对抗炎活性起着重要作用。     

Use of pulse oximetry for blood pressure measurement after cardiac surgery

Blood pressure measurement using pulse oximeter waveform change was compared with an oscillometric measurement and the gold standard, intra-arterial measurement, in children after cardiac surgery. Forty six patients were enrolled and divided into groups according to weight. Simultaneous blood pressure measurements were obtained from the arterial catheter, the oscillometric device, and the pulse oximeter. Pulse oximeter measurements were obtained with a blood pressure cuff proximal to the oximeter probe. The blood pressure measurements from the pulse oximeter method correlated better with intra-arterial measurements than those from the oscillometric device (0.77-0.96 v 0.42-0.83). The absolute differences between the pulse oximeter and intra-arterial measurements were significantly smaller than between the oscillometric and intra-arterial measurements in children less than 15.0 kg. The pulse oximeter waveform change is an accurate and reliable way to measure blood pressure in children non-invasively, and is superior to the oscillometric method for small patients.     

Granulomatous inflammation in Acanthamoeba sclerokeratitis

This report describes the histopathological findings in a patient with Acanthamoeba sclerokeratitis (ASK). A 58-year-old patient with ASK underwent enucleation and sections of the cornea and sclera were subjected to histopathology and immunohistochemistry with monoclonal mouse antihuman antibodies against T cell CD3 and B cell CD20 antigens. Hematoxylin and Eosin stained sections of the cornea revealed epithelial ulceration, Bowman''s membrane destruction, stromal vascularization, infiltration with lymphocytes, plasma cells, and granulomatous inflammation with multinucleated giant cells (MNGC). The areas of scleritis showed complete disruption of sclera collagen, necrosis and infiltration with neutrophils, macrophages, lymphocytes, and granulomatous inflammation with MNGC. No cyst or trophozoites of Acanthamoeba were seen in the cornea or sclera. Immunophenotyping revealed that the population of lymphocytes was predominantly of T cells. Granulomatous inflammation in ASK is probably responsible for the continuance and progression of the scleritis and management protocols should include immunosuppressive agents alongside amoebicidal drugs.     

Monocyte chemoattractant protein-1 plays a critical role in neuroblast migration after focal cerebral ischemia.

Transient focal ischemia is known to induce proliferation of neural progenitors in adult rodent brain. We presently report that doublecortin positive neuroblasts formed in the subventricular zone (SVZ) and the posterior peri-ventricle region migrate towards the cortical and striatal penumbra after transient middle cerebral artery occlusion (MCAO) in adult rodents. Cultured neural progenitor cells grafted into the non-infarcted area of the ipsilateral cortex migrated preferentially towards the infarct. As chemokines are known to induce cell migration, we investigated if monocyte chemoattractant protein-1 (MCP-1) has a role in post-ischemic neuroblast migration. Transient MCAO induced an increased expression of MCP-1 mRNA in the ipsilateral cortex and striatum. Immunostaining showed that the expression of MCP-1 was localized in the activated microglia and astrocytes present in the ischemic areas between days 1 and 3 of reperfusion. Furthermore, infusion of MCP-1 into the normal striatum induced neuroblast migration to the infusion site. The migrating neuroblasts expressed the MCP-1 receptor CCR2. In knockout mice that lacked either MCP-1 or its receptor CCR2, there was a significant decrease in the number of migrating neuroblasts from the ipsilateral SVZ to the ischemic striatum. These results show that MCP-1 is one of the factors that attract the migration of newly formed neuroblasts from neurogenic regions to the damaged regions of brain after focal ischemia.     

A contrast correction method for dental images based on histogram registration

Contrast correction is often required in digital subtraction radiography when comparing medical data acquired over different time periods owing to dissimilarities in the acquisition process. This paper focuses on dental radiographs and introduces a novel approach for correcting the contrast in dental image pairs.The proposed method modifies the subject images by applying typical registration techniques on their histograms. The proposed histogram registration method reshapes the histograms of the two subject images in such a way that these images are matched in terms of their contrast deviation. The method was extensively tested over 4 sets of dental images, consisting of 72 registered dental image pairs with unknown contrast differences as well as 20 dental pairs with known contrast differences. The proposed method was directly compared against the well-known histogram-based contrast correction method.The two methods were qualitatively and quantitatively evaluated for all 92 available dental image pairs. The two methods were compared in terms of the contrast root mean square difference between the reference image and the corrected image in each case. The obtained results were also verified statistically using appropriate t-tests in each set.The proposed method exhibited superior performance compared with the well-established method, in terms of the contrast root mean square difference between the reference and the corrected images. After suitable statistical analysis, it was deduced that the performance advantage of the proposed approach was statistically significant.